PELICAN SUMMARY – September, 2013

Q1: What was the purpose of the PELICAN study?

A: The primary aim of the study was to demonstrate that levels of placental growth factor (PlGF) in
pregnant women presenting with suspected, but unconfirmed, pre-eclampsia are predictive of a final
confirmed diagnosis of pre-eclampsia and pregnancy outcome (requirement to deliver preterm).

Q2: When and where did the PELICAN study take place?

A: Seven consultant-led maternity units in the British Isles were involved with the study. Plasma samples
were collected from 625 pregnant women, enrolled and data analysed between March 2011 and
September 2012.

Q3: How were samples collected and analysed?

A: Women presenting between 20+0 and 40+6 weeks’ gestation with suspected pre-eclampsia were
invited to participate in the study; those already diagnosed with pre-eclampsia or less than 16 years old
were excluded.

Q4: What was the main outcome of the study?

A: The Alere Triage® PLGF test had high sensitivity (96%) and high negative predictive value (98%) for
pre-eclampsia in women presenting to clinic with suspected pre-eclampsia before 35 weeks’ gestation.
PlGF was a better predictor of pregnancy outcome than standard tests (i.e., blood pressure, proteinuria,
liver enzymes, and uric acid) used singularly or in combination.

Q5: Why should clinicians consider using PlGF?

A: PlGF accurately detects placental dysfunction in women with signs or symptoms of pre-eclampsia
before 35 weeks’ gestation1,2. Signs or symptoms might be limited to isolated hypertension, proteinuria,
fetal growth restriction or other features which raise the suspicion of evolving pre-eclampsia, but do not
diagnose the condition or accurately predict adverse outcomes3,4,5.

Follow-up points:

1. Hypertension and proteinuria can be caused by other conditions needing a different management
pathway. Low PlGF identifies the probable “cause” (i.e., placental dysfunction) of the clinical findings
and is a better predictor of pregnancy outcome1.

2. Placental dysfunction can lead to different pregnancy complications (e.g., HELLP Syndrome, Eclampsia,
fetal growth restriction, placental abruption, and stillbirth)6. Prediction of these outcomes using clinical
assessment and laboratory tests alone is poor and can lead to over-management in some women and
delayed or missed detection in others7,8.

3. PlGF is more predictive of a need for delivery than other commonly utilised signs and tests, used on
their own or in combination. PlGF measured at first presentation accurately detects placental
dysfunction in women who might progress to a serious adverse perinatal outcome (e.g. intrauterine
death) and missed by current tests1,9.
 PELICAN SUMMARY – September, 2013

Q6: How might PlGF change clinical management?

A: Clinical uncertainty leads to unnecessary referral, over-utilisation of fetal and maternal assessments,
and inappropriate hospital admission for diagnostic testing or expectant management10. PlGF will help
stratify women into those needing urgent referral and those at very low risk for adverse perinatal
outcome.

Follow-up points:

1. PlGF below 12 pg/mL is considered highly abnormal and suggestive of severe placental dysfunction.
These women have a median time-to-delivery of 9 days and need urgent assessment in a setting
equipped for early preterm delivery11.

2. PlGF above 100 pg/mL is considered normal and suggestive of the absence of placental dysfunction.
These women have a median time-to-delivery of 61 days and are unlikely to need delivery for pre-
eclampsia in the next 14 days.

3. PlGF between 12 and 100 pg/mL is considered abnormal and suggestive of the presence of placental
dysfunction. These women have a median time-to-delivery of 23 days and should be considered for
close follow-up.

Q7: What effect might PlGF have on patient outcomes?

A: Introduction of PlGF assessment will improve risk stratification, achieve an earlier diagnosis based
upon pathologically relevant changes, and allow individualised management of women with different
levels of disease severity.

Follow-up points:

1. There is potential to reduce associated maternal morbidity by detecting placental dysfunction before
onset of severe disease. Identifying risk to the fetus and implementing appropriate assessment and
monitoring might reduce adverse perinatal outcome.

2. PlGF has a high sensitivity (96%) for the detection of the different forms of pre-eclampsia and accurately
stratifies them into women requiring urgent investigation and planned delivery and women requiring
close follow-up1,9,11.

3. Importantly, PlGF accurately detects an underlying disease process and predicts an adverse outcome in
women who do not progress to meet a final diagnosis of pre-eclampsia. By example, all cases of
potentially avoidable stillbirth in the PELICAN study were in women who had final diagnoses of
gestational hypertension or chronic hypertension, inappropriately placing them at low risk.
Measurement of PlGF in these women would have identified placental dysfunction and might have
avoided an adverse outcome.

Q8: How can clinicians justify implementation of PlGF?

A: Unnecessary referral, testing, and intervention associated with antenatal monitoring and in-patient
hospital admissions, places considerable burden on health systems. Implementation of PlGF will help
target resources to those at highest risk, therefore reducing morbidity, while minimising excessive
assessment and intervention in women at lower risk.
 PELICAN SUMMARY – September, 2013

Follow-up points:

1. Forty-two per cent of women with suspected pre-eclampsia before 35 weeks’ gestation are identified as
very low risk for required delivery within 14 days of the test. This allows antenatal monitoring to be
reduced and referral or hospital admission to be avoided.

2. Twenty four per cent of women will be identified, appropriately and with sufficient notice, as high risk
for an adverse outcome, creating the possibility for reduced adverse outcomes such as severe pre-
eclampsia and placentally-mediated stillbirth by planned intrvention.

3. Mean cost saving associated with the clinical algorithm integrating PlGF is £35,647 per 1,000 pregnant
women or a cost saving of £582 per woman given a PlGF test. There is a 94% probability that PlGF plus
the risk algorithm is cost saving compared to usual treatment based on the values used in the model.12 .
References:

1. INSERT PELICAN PUBLICATION.

2. Sibiude J, Guibourdenche J, Dionne MD, et al. Placental growth factor for the prediction of adverse outcomes in patients with
suspected preeclampsia or intrauterine growth restriction. PloS one. 2012;7(11):e50208.

3. Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia-eclampsia. American journal of obstetrics and
gynecology. 2009 May;200(5):481 e1-7.

4. Sibai BM. Imitators of severe preeclampsia. Obstetrics and gynecology. 2007 Apr;109(4):956-66.

5. Zhang J, Klebanoff MA, Roberts JM. Prediction of adverse outcomes by common definitions of hypertension in pregnancy.
Obstetrics and gynecology. 2001 Feb;97(2):261-7.

6. Staff AC, Benton SJ, von Dadelszen P, et al. Redefining Preeclampsia Using Placenta-Derived Biomarkers. Hypertension. 2013.

7. Anumba DO, Lincoln K, Robson SC. Predictive value of clinical and laboratory indices at first assessment in women referred with
suspected gestational hypertension. Hypertension in pregnancy : official journal of the International Society for the Study of
Hypertension in Pregnancy. 2010 Jan;29(2):163-79.

8. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. American
journal of obstetrics and gynecology. 2000 Jul;183(1):S1-S22. PubMed PMID: 10920346. Epub 2000/08/02.

9. Chappell L et al. OP007. PlGF in combination with other commonly utilized tests and other biomarkers for predicting the need for
pre-eclampsia within 14 days in women presenting prior to 35 weeks’ gestation. Pregnancy Hypertension. Volume 3. Number 2.
April 2013.

10. Opie H, Snyder TE. Hypertension in pregnancy: preeclampsia-eclampsia. Kansas medicine : the journal of the Kansas Medical
Society. 1993 Apr;94(4):105-9.

11. Alere Triage® PLGF Test Product Insert

12. Budget impact analysis of the Triage® PlGF test for women < 35 weeks gestation with suspected but not diagnosed pre-
eclampsia. Rachael Hunter, Senior Research Associate (Health Economics), UC